Method for producing 1 substituted 5-chloro-4 methly pyrazoles

ABSTRACT

The present invention relates to a process for preparing 1-substituted 5-chloro-4-methylpyrazoles of the general formula I                  
 
with the meaning for R stated in claim  1 , in which a 4-methylpyrazole of the formula II                  
 
is reacted with chlorine, the resulting mixture of monochlorinated and dichlorinated product is fractionated by distillation, and subsequently the dichlorinated compound is dehalogenated to compound II and returned to the reaction with chlorine.

The present invention relates to a process for preparing N-substituted5-chloro-4-methylpyrazoles of the general formula I

in which

-   R is C₁–C₈-alkyl or C₅–C₁₀-cycloalkyl, each of which optionally has    one or more substituents.

1-Alkyl-4-methyl-5-chloropyrazoles are important starting materials forpreparing pharmaceuticals and crop protection agents.

EP 0366 329 A1 describes the preparation of 5-halo-4-methylpyrazoles and3,5-dihalo-4-methylpyrazoles by reacting 4-methylpyrazoles with halogen.

The process described in EP 0366 329 A1 has the disadvantage that thechlorination results in a mixture of monochlorinated and dichlorinatedcompounds. This means that part of the valuable starting material islost in the form of the dichlorinated pyrazole, and the yield of5-chloro-4-methylpyrazole I, based on the 4-methylpyrazole compound IIemployed, is only moderate. It is an object of the present invention toprovide an economic process for preparing 5-chloro-4-methylpyrazoles ofthe formula I which affords the target compound in better yields basedon the 4-methylpyrazole compound employed as starting material.

We have found that this object is achieved by a process in whichinitially a 4-methylpyrazole compound is reacted with chlorine, thereaction product is fractionated into the monochloropyrazole anddichloropyrazole, and the dichloropyrazole is dehalogenated and returnedto the reaction with chlorine.

Accordingly, the present invention relates to a process for preparing1-substituted 5-chloro-4-methylpyrazoles of the formula I by reacting a4-methylpyrazole compound of the formula II

in which R has the abovementioned meanings, with chlorine, resulting ina mixture of compound I and a 1-substituted3,5-dichloro-4-methylpyrazole compound of the formula III

in which R has the aforementioned meanings, wherein the compound III isseparated from the compound I, the compound III is dehalogenated to givethe compound II, and the latter is reacted anew with chlorine.

The 5-chloro-4-methylpyrazoles I which can be obtained in a high overallyield in the process of the invention can additionally be converted intoN-substituted 2-pyrazolin-5-ones, which are likewise valuableintermediates for the preparation of pharmaceuticals and crop protectionagents. A further aspect of the present invention is therefore theprovision of a process for preparing N-substituted 2-pyrazolin-5-onesstarting from 1-substituted 5-chloro-4-methylpyrazoles of the formula I.

The nature of the substituent R is of minor importance in the presentinvention. Meanings are thus:

C₁–C₈-Alkyl: a linear or branched alkyl chain with 1 to 8 C atoms, e.g.methyl, ethyl, n-propyl, isopropyl, n-butyl, 2-butyl, isobutyl,tert-butyl, n-pentyl, 2-methylbutyl, 2,2-dimethylpropyl, n-hexyl,1-methylpentyl, 2-methylpentyl, 1-ethylbutyl, 2-ethylbutyl, n-heptyl,o-octyl and 2-ethylhexyl.

C₅–C₁₀-Cycloalkyl: mono- or bicyclic hydrocarbon radicals with 5 to 10carbon atoms, e.g. cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl,cyclononyl, cyclodecyl, norbornyl, bicyclo[2.2.2]octyl anddecahydronaphthyl.

The aforementioned radicals may have one or more substituents. Examplesof such radicals are halogen such as fluorine or chlorine, haloalkylsuch as trifluoromethyl, pentafluoroethyl and fluoroalkoxy such astrifluoromethoxy and pentafluoroethoxy. Cycloalkyl is also suitable forthe radical.

The starting materials of the formula II are known and available to theskilled worker (see, for example, EP 0 366 329 A1 and literature citedtherein).

The reaction of the 4-methylpyrazoles II with chlorine takes place bymethods customary for a chlorination of pyrazoles, e.g. by the methoddescribed in EP 366 329 A1, which is incoporated herein by reference.The chlorination is preferably carried out in an inert organic solvent.Examples of solvents used are halogenated aliphatic hydrocarbons such as1,2-dichloroethane, dichloromethane, dichloropropane, 1-chloropentane.

The reaction temperature is generally between room temperature and theboiling point of the solvent and is kept in the range from about 40° C.to about 70° C.

Compound II is normally reacted with chlorine in such a way that asufficient amount of chlorine is added at the required reactiontemperature to a reaction vessel containing compound II. Addition cantake place either in the form of a chlorine-containing solution,preferably in one of the aforementioned solvents, or else by passing inchlorine gas. Chlorine is mostly employed in excess relative to thepyrazole II, with the aim of complete reaction. This excess ispreferably up to 70 mol %, in particular 10–60 mol %. A largerproportion of dichloro compound does not interfere subsequently becausein the process of the invention the dichloropyrazole is dehalogenatedand returned to the reaction with chlorine.

The reaction mixture resulting from the chlorination is worked up in aconventional way and the mixture of monochloro compound I and dichlorocompound III which results in a yield of >95% based on compound IIemployed, is fractionated, e.g. by fractional distillation, preferablyunder reduced pressure. This results in compound I in a pure form whichcan be further processed immediately. According to the invention,compound III, where appropriate mixed with compound I, is thendehalogenated to give compound II.

The dehalogenation of III or of a mixture of compounds I and III takesplace by processes conventional for this purpose. A review of variousdehalogenation processes is to be found in Chem. Technik 6 (1994)316–323 and the literature cited therein.

The dehalogenation of a compound III preferably takes place by catalytichydrogenolysis. The partial pressure of hydrogen is in the range fromabout 1 bar to about 80 bar, in particular in the range from about 10bar to about 80 bar, especially in the range from about 10 bar to about50 bar. The dechlorination normally takes place at elevated temperature,preferably between about room temperature and about 150° C., inparticular between about 50° C. and about 100° C. The reaction timedepends, as expected, on the chosen reaction conditions and on thecompound III used.

The catalysts employed for the hydrogenolysis will normally betransition metals and their compounds or complexes, preferably employingthe catalysts in supported form. Particularly preferred transitionmetals are the metals of group VIII and, very particularly, the platinummetals such as palladium, rhodium and platinum.

Suitable support materials include both inorganic supports such astitanium dioxide, silica gel, silica, zeolites, alumina and organicpolymers or activated carbon. In a preferred embodiment of theinvention, palladium on activated carbon is used as catalyst.

To trap the hydrogen chloride formed, the hydrogenolysis is preferablycarried out in the presence of a suitable base such as a tertiary amine,for example triethylamine, or a basic salt such as an alkali metalacetate or alkaline earth metal acetate, in particular sodium acetate,or such as an alkali metal carbonate or alkali metal bicarbonate, suchas sodium carbonate or sodium bicarbonate. Other suitable bases arealkali metal hydroxides such as sodium hydroxide or potassium hydroxideand alkaline earth metal hydroxides such as calcium hydroxide ormagnesium hydroxide. Also suitable are alkaline earth metal oxides suchas calcium oxide or magnesium oxide. Preferably at least 2 mol of baseare employed per mol of the compound III, because two mol of hydrogenchloride must be neutralized.

The dehalogenation is preferably carried out in an organic solvent.Particularly suitable are the starting material II, aliphaticC₁–C₈-carboxylic acids such as formic acid, acetic acid, ropanoic acid,pivalic acid, butyric acid and mixtures thereof, specially acetic acid,or solvents which are stable under the reaction conditions, such asethers, for example tetrahydrofuran, ioxane, carboxylic esters such asacetic esters, aromatic hydrocarbons such as toluene or aliphatichydrocarbons. In a preferred embodiment, glacial acetic acid and/or thestarting material II is used as solvent.

Working up the reaction mixture obtained from the dehalogenation byconventional processes results in the 4-methylpyrazole of the formulaII, which is then subjected to chlorination anew.

The process of the invention thus makes it possible to convert thepyrazoles of the general formula II into the 5-chloro-4-methylpyrazolesof the general formula I in high yields.

The 5-chloro-4-methylpyrazoles of the formula I are obtained by theprocess of the invenetion are of particular interest in relation to thesynthesis of N-substituted 2-pyrazolin-5-ones of the general formula IV

in which R is as defined above. This is because the applicant has foundthat the 4-methyl group in the compounds of the formula I can bedegraded and, at the same time, the 5-chloro functionality can beconverted into a hydroxyl group. The 5-hydroxypyrazole resulting fromthis is a tautomer of IV and accordingly rearranges into compound IV oris in equilibrium therewith.

Conversion of the 5-chloro-4-methylpyrazole takes place according to theinvention by oxidizing the methyl group in the 4 position to thecarboxyl group, and reacting the 4-carboxy-5-chloropyrazole of theformula V obtained in this way and in which R has the aforementionedmeanings with a molar excess of alkali metal hydroxide in an aqueousreaction medium at elevated temperature, and subsequently adjusting a pHof ≦6 in the aqueous reaction medium by adding an acid.

Processes for oxiding aromatic methyl groups to carboxyl groups areknown in the prior art, for example from EP 224 094, U.S. Pat. No.3,801,584 and EP 350 176 A.

N-substituted 5-halo-4-methylpyrazoles are preferably oxidized by theprocess described in EP-A 350 176 in a simple manner to the carboxylicacids of the formula V.

The oxidation preferably takes place using hydrogen peroxide and/oroxygen. The source of oxygen used is pure oxygen or air, with thepartial pressure of the oxygen-containing gas normally being about 1 to93 bar. The oxidation preferably took place by reacting I withatmospheric oxygen in the presence of a transition metal compound or ofa transition metal salt in which the transition metal is present in anoxidation state >0.

Suitable transition metal salts are salts of manganese, cobalt, iron andmixtures thereof, such as iron formate, iron acetate, iron lactate, ironoxalate, iron octylate, iron acetylacetonate, iron chloride, ironbromide, iron iodide, cobalt formate, cobalt acetate, cobalt octylate,cobalt acetylacetonate, cobalt iodide, cobalt carbonate, manganeseformate, manganese acetate, manganese octylate, manganeseacetylacetonate, manganese chloride, manganese bromide, manganese iodideand manganese carbonate.

The oxidation is preferably carried out in the presence of bromide ions,e.g. in the form of an alkaline earth or alkali metal bromide such assodium bromide, potassium bromide or ammonium bromide.

The solvents normally used are a lower carboxylic acid such as aceticacid, propionic acid, butyric acid or a lower carboxylic anhydride suchas acetic anhydride or propionic anhydride. The reaction temperature isusually in the range from about 20 to about 200° C.

To convert V into the pyrazolone IV in the process of the invention, ina first step a compound of the formula V is reacted with alkali metalhydroxide in molar excess in an aqueous reaction medium. A molar excessof alkali metal hydroxide is ensured with compounds of the generalformula V when more than 2 mol of alkali metal hydroxide are employedper mol of compound V. In the first stage, one mol is required forreplacing Cl by hydroxyl, and one mol is required for neutralizing thecarboxylic acid. It is preferred according to the invention to employ 3to 20 mol of alkali metal hydroxide and, in particular, 5 to 12 mol ofalkali metal hydroxide per mol of compound V. Preferred alkali metalhydroxides are sodium hydroxide and potassium hydroxide, in particularsodium hydroxide.

Suitable aqueous reaction media are both water and mixtures of water andwater-miscible organic solvents. The water-miscible organic solvents arepreferably inert toward alkali metal hydroxide under the reactionconditions. Examples of suitable organic solvents are C₁–C₄-alkanols, inparticular methanol and ethanol, and additionally dimethyl sulfoxide,tetrahydrofuran, dioxane, glycol, glycerol, diethylene glycol,triethylene glycol and the like. The aqueous reaction medium willusually contain not more than 50% by volume, preferably not more than30% by volume, and in particular not more than 10% by volume, of awater-miscible organic solvent. In a preferred embodiment of the presentinvention, water is the sole solvent.

The first reaction step is particularly preferably carried out in anaqueous alkali metal hydroxide solution containing 10 to 50% by weightand, in particular, 20 to 40% by weight of alkali metal hydroxide.

The first reaction step is carried out according to the invention atelevated temperature. Elevated temperature means heating to, normally,at least 50° C. and preferably at least 90° C. The reaction temperaturewill normally not exceed 200° C. The reaction is very particularlypreferably carried out at temperatures in the range from 120 to 200° C.

The first reaction step is carried out under atmospheric pressure orelevated pressure depending on the reaction temperature. At reactiontemperatures above 100° C., a reaction pressure of from 1 to 10 bar isnormally set up. Typical reaction conditions are, for example with apurely aqueous reaction medium, 150 to 180° C. and 5 to 7 bar.

The reaction will normally lead to almost complete conversion of thestarting material V. Conversion means here the transformation of Cl inthe pyrazole V into a hydroxyl group or the formation of thecorresponding alcoholate. The time taken to reach virtually completeconversion depends, of course, on the chosen reaction conditions and mayvary between 0.5 h and 24 h. Typical reaction times in purely aqueoussystems are normally in the range from 2 to 10 h.

In the second reaction step, the product obtained in the first reactionstep is reacted under acidic conditions. This involves formation of thecompound IV with evolution of CO₂. The CO₂ evolution is attributable tothe elimination of the carboxyl group present in the 4 position on thepyrazole ring.

The second reaction stage is normally carried out without isolation ofthe product formed in the first reaction stage. The second reactionstage is preferably initiated by adding an acid to the reaction mixturefrom the first reaction stage. It is also possible where appropriate toremove partially or completely the aqueous solvent for the firstreaction stage before carrying out the second reaction stage and replaceit by a new solvent, preferably an aqueous solvent and, in particular,by water. This procedure is particularly suitable when there has beenuse in the first stage of an organic solvent which, for example, impedesisolation of the compound IV because of a volatility comparable theretoor in any other way.

The second reaction stage is carried out according to the inventionunder acidic conditions, i.e. the pH of the reaction mixture in thesecond reaction stage is at most 6 and is preferably in the range from 1to 3. The pH is preferably not below 0. The pH is adjusted by adding anacid to the product of the first reaction stage. The acid is preferablygiven to the aqueous reaction mixture from the first reaction stage. Theprocedure will normally be such that the reaction mixture from the firstreaction stage is cooled to a temperature suitable for the secondreaction stage, which is normally in the range from about 0 to 100° C.and is preferably in the range from about 10 to 50° C., and then theacid is added.

Suitable acids are in principle all acids which have an acidic strengthsufficient to reach the desired pH. If the second reaction stage iscarried out immediately following the first reaction stage, account mustbe taken of the fact that excess alkali metal hydroxide must beneutralized. For this reason, a strong acid, preferably a mineral acidsuch as hydrochloric acid, sulfuric acid or phosphoric acid, will beemployed to adjust the pH. The acids and, in particular, hydrochloricacid, phosphoric acid and sulfuric acid are preferably employed in adilute aqueous form.

If the first reaction stage is carried out under pressure, it isadvisable to decompress the reactor before neutralization with the acid.The decarboxylation usually starts spontaneously on addition of the acidwhen the suitable pH is reached. If desired, the reaction conditions canalso be maintained for a certain period, which may be from a few minutesup to some hours, to complete the decarboxylation. Compound IV isisolated in a conventional way by working up the reaction mixtures fromthe second reaction step by conventional workup methods, for example byextractive workup of the liquid reaction mixture with an organic solventor by removing the solvent and isolating the target compound from theresidue obtained thereby. Before the workup it is advisable toneutralize the reaction mixture from the second reaction stage with abase to pH values of ≧6, e.g. pH 6 to 7. Suitable bases are alkali metalhydroxides, alkali metal carbonates, alkali metal bicarbonates, alkalineearth metal carbonates and alkaline earth metal hydroxides. Alkali metalhydroxides and, in particular, sodium hydroxide will normally beemployed for the neutralization.

Because of the salt content resulting in the process of the invention,it is frequently advantageous for isolating the compound IV to removesubstantially or completely the aqueous reaction medium from the 2^(nd)reaction stage, preferably after neutralization, by distillation or byevaporation in vacuo, and to extract the residue with a suitable organicsolvent. The solvent chosen for this by the skilled worker will dissolvethe desired product but not the salts resulting from the neutralization.Typical organic solvents for the extraction are C₂–C₆-alcohols such asethanol, n-propanol, isopropanol, n-butanol, isobutanol, amyl alcoholand isoamyl alcohol, aromatic hydrocarbons such as toluene, ethylbenzeneand xylenes. Evaporation of the extract to dryness results in the targetcompound IV, which can be further purified and worked up in aconventional way.

It is likewise possible to work up the aqueous reaction medium from the2^(nd) reaction stage, preferably after neutralization, by extractionwith a polar solvent which is immiscible or of only limited miscibilitywith water, for example by extraction with a C₄–C₆-alcohol such asn-butanol, isobutanol, amyl alcohol or isoamyl alcohol, or with one ofthe aforementioned aromatic hydrocarbons. The extraction can be carriedout in portions or continuously.

To illustrate the process of the invention, a typical process method forconverting the compounds II into a 2-pyrazolin-5-ones is describedbelow:

The compounds V are dissolved in an aqueous solution of the alkali metalhydroxide. The concentration of the solution is usually in the rangefrom 10 to 50% by weight and is at a level such that 5 to 12 mol ofalkali metal hydroxide are present per mol of compound V. This solutionis heated in an autoclave to a temperature in the range from 150 to 180°C., setting up a pressure in the range from 5 to 7 bar. The reactiontemperature is maintained for 2 to 10 hours. After cooling to roomtemperature and decompression to atmospheric pressure, a sufficientamount of mineral acid to adjust the pH is added. The pH is preferablyin the range from 0 to 6 and, in particular, in the range from 1 to 3.Spontaneous CO₂ evolution occurs at this point. A base is then used toneutralize to pH 6 to 7. The reaction mixture is evaporated to drynessin vacuo, and the solid residue is extracted, for example in a Soxhletapparatus, with a suitable solvent. Evaporation of the solvent resultsin the N-substituted 2-pyrazolin-5-one of the formula IV in high yieldand purity. In place of evaporation/extraction it is possible to isolatethe compound IV from the aqueous reaction mixture after neutralizationto pH 6 to 7 also by extraction with a suitable solvent, e.g. isobutanolor toluene.

To illustrate the process of the invention, a typical process method forconverting the compounds of the general formula II into theN-substituted 5-chloro-4-methylpyrazoles of the general formula I,subsequent oxidation thereof to a compound of the general formula V, andthe conversion of the compounds V into the N-substituted2-pyrazolin-5-ones of the general formula IV is described below. Theseexamples serve only for illustration and are not to be regarded asrestrictive.

EXAMPLE 1 Chlorination of 1,4-dimethylpyrazole

190 g (2.67 mol) of chlorine were passed into a solution of 192 g (2.0mol) of 1,4-dimethylpyrazole and 800 g of 1,2-dichloroethane over thecourse of 2 h. The temperature rose to 60° C. and could be kept at 60°C. by cooling with ice. While cooling, the resulting reaction mixturewas neutralized at 25° C. with 650 g (2.43 mol) of 15% strength aqueoussodium hydroxide solution. After phase separation, the organic phase wasdistilled to afford 170.1 g (1.3 mol) of 5-chloro-1,4-dimethylpyrazoleof boiling point (120) 105° C. and a purity of 99.7% (GC) and 99.3 g(0.6 mol) of 3,5-dichloro-1,4-dimethylpyrazole of boiling point (15) 85°C. and a purity of 99.5% (GC). The yields of5-chloro-1,4-dimethylpyrazole and 3,5-dichloro-1,4-dimethylpyrazoleresulted in an overall yield of 95% based on 1,4-dimethylpyrazole.

EXAMPLE 2 Dehalogenation of 3,5-dichloro-1,4-dimethylpyrazole in glacialacetic acid

12.5 g (0.075 mol) of 3,5-dichloro-1,4-dimethylpyrazole with a purity of99.5%, 150 g of 100% pure acetic acid, 12.3 g (0.15 mol) of sodiumacetate and 6.3 g of 10% Pd/C catalyst were heated to 60° C. in a 350 mlstirred autoclave. 30 bar of hydrogen were injected at this temperature.The reaction started immediately and hydrogen uptake was complete afterabout 3 h. The autoclave was allowed to cool to 25° C. and wasdecompressed, and the catalyst and the produced sodium chloroid werefiltered off. Distillation of the filtrate afforded 6.86 g of1,4-dimethylpyrazole of boiling point 151° C. and a purity of 99.7%(GC). This corresponds to a yield of 95% of theory.

EXAMPLE 3 Dehalogenation of 3,5-dichloro-1,4-dimethylpyrazole in1,4-dimethylpyrazole in the presence of sodium acetate

16.6 g (0.1 mol) of 3,5-dichloro-1,4-dimethylpyrazole with a purity of99.5%, 50 g of 99.8% pure 1,4-dimethylpyrazole, 16.4 g (0.2 mol) ofsodium acetate and 6.4 g of 30% Pd/C catalyst were heated to 80° C. in a350 ml stirred autoclave. 40 bar of hydrogen were injected at thistemperature. Hydrogen uptake was complete after about 6 h. The autoclavewas allowed to cool to 25° C. and was decompressed, and the catalyst andproduced sodium chloride were filtered off. Distillation of the filtrateafforded 59 g of 1,4-dimethylpyrazole of boiling point 151° C. and apurity of 99.8%. Subtracting the 50 g of 1,4-dimethylpyrazole employedas solvent, this corresponds to a yield of 93.6% of theory.

EXAMPLE 4 Dehalogenation of 3,5-dichloro-1,4-dimethylpyrazole in1,4-dimethylpyrazole in the presence of sodium hydroxide solution

16.6 g (0.1 mol) of 3,5-dichloro-1,4-dimethylpyrazole with a purity of99.5%, 50 g of 99.8% pure 1,4-dimethylpyrazole, 16.0 g (0.2 mol) of 50%by weight sodium hydroxide solution and 6.4 g of 30% Pd/C catalyst wereheated to 80° C. in a 350 ml stirred autoclave. 40 bar of hydrogen wereinjected at this temperature. Hydrogen uptake was complete after about 6h. The autoclave was allowed to cool to 25° C. and was decompressed, andthe catalyst and produced sodium chloride were filtered off.Distillation of the filtrate afforded 58.7 g of 1,4-dimethylpyrazole ofboiling point 151° C. and a purity of 99.8%. Subtracting the 50 g of1,4-dimethylpyrazole employed as solvent, this corresponds to a yield of90.0% of theory.

EXAMPLE 5 Dehalogenation of 3,5-dichloro-1,4-dimethylpyrazole in1,4-dimethylpyrazole in the presence of calcium hydroxide

16.6 g (0.1 mol) of 3,5-dichloro-1,4-dimethylpyrazole with a purity of99.5%, 50 g of 99.8% pure 1,4-dimethylpyrazole, 7.4 g (0.1 mol) ofcalcium hydroxide, 8 ml of water and 6.4 g of 30% Pd/C catalyst wereheated to 80° C. in a 350 ml stirred autoclave. 40 bar of hydrogen wereinjected at this temperature. Hydrogen uptake was complete after about 6h. The autoclave was allowed to cool to 25° C. and was decompressed, andthe catalyst and produced calcium chloride were filtered off.Distillation of the filtrate afforded 58.2 g of 1,4-dimethylpyrazole ofboiling point 151° C. and a purity of 99.7%. Subtracting the 50 g of1,4-dimethylpyrazole employed as solvent, this corresponds to a yield of84.6% of theory.

EXAMPLE 6 Dehalogenation of 3,5-dichloro-1,4-dimethylpyrazole in1,4-dimethylpyrazole in the presence of calcium oxide

16.6 g (0.1 mol) of 3,5-dichloro-1,4-dimethylpyrazole with a purity of99.5%, 50 g of 99.8% pure 1,4-dimethylpyrazole, 5.6 g (0.1 mol) ofcalcium oxide, 8 ml of water and 6.4 g of 30% Pd/C catalyst were heatedto 80° C. in a 350 ml stirred autoclave. 40 bar of hydrogen wereinjected at this temperature. Hydrogen uptake was complete after about 6h. The autoclave was allowed to cool to 25° C. and was decompressed, andthe catalyst and produced calcium chloride were filtered off.Distillation of the filtrate afforded 57.6 g of 1,4-dimethylpyrazole ofboiling point 151° C. and a purity of 99.7%. Subtracting the 50 g of1,4-dimethylpyrazole employed as solvent, this corresponds to a yield of78.4% of theory.

EXAMPLE 7 Chlorination of 1-ethyl-4-methylpyrazole

167.7 g (2.36 mol) of chlorine were passed into a solution of 165 g (1.5mol) of 1-ethyl-4-methylpyrazole and 625 g of 1,2-dichloroethane overthe course of 2 h. The temperature rose to 60° C. and could be kept at60° C. by cooling with ice. While cooling, the resulting reactionsolution was neutralized at 25° C. with 533.9 g (2.0 mol) of 15%strength aqueous sodium hydroxide solution. After phase separation, theorganic phase was distilled to afford 122.1 g (0.843 mol) of5-chloro-1-ethyl-4-methylpyrazole of boiling point (200) 118° C. and apurity of 99.8% (GC) and 109.1 g (0.61 mol) of3,5-dichloro-1-ethyl-4-methylpyrazole of boiling point (200) 154° C. anda purity of 99.6%. This corresponds to a yield of 96.6% of theory basedon 1-ethyl-4-methylpyrazole.

EXAMPLE 8 Dehalogenation of 3,5-dichloro-1-ethyl-4-methylpyrazole inglacial acetic acid

18.0 g (0.1 mol) of 3,5-dichloro-1-ethyl-4-methylpyrazole with a purityof 99.6%, 100 g of 100% pure acetic acid, 16.4 g (0.2 mol) of sodiumacetate and 8.4 g of 10% Pd/C catalyst were heated to 80° C. in a 350 mlstirred autoclave. 20 bar of hydrogen were injected at this temperature.The reaction started immediately and hydrogen uptake was complete afterabout 2 h. The autoclave was allowed to cool to 25° C. and wasdecompressed, and the catalyst and the produced sodium chloride werefiltered off. Distillation of the filtrate afforded 10.3 g of1-ethyl-4-methylpyrazole of boiling point 158° C. and purity 99.6% (GC).This corresponds to a yield of 93.4% of theory.

EXAMPLE 9 Dehalogenation of 3,5-dichloro-1-ethyl-4-methylpyrazole in1-ethyl-4-methylpyrazole

18.0 g (0.1 mol) of 3,5-dichloro-1-ethyl-4-methylpyrazole with a purityof 99.6%, 50 g of 1-ethyl-4-methylpyrazole with a purity of 99.8%, 16.4g (0.2 mol) of sodium acetate and 6.4 g of 30% Pd/C catalyst were heatedto 80° C. in a 350 ml stirred autoclave. 30 bar of hydrogen wereinjected at this temperature. Hydrogen uptake was complete after about 4h. The autoclave was allowed to cool to 25° C. and was decompressed, andthe catalyst and the produced sodium chloroide were filtered off.Distillation of the filtrate afforded 60.4 g of 1-ethyl-4-methylpyrazoleof boiling point 158° C. and purity 99.7%; subtracting the 50 g of1-ethyl-4-methylpyrazole employed, this corresponds to a yield of 93.6%of theory.

EXAMPLE 10 Oxidation of 5-chloro-1,4-dimethylpyrazole

43.1 g (0.33 mol) of 5-chloro-1,4-dimethylpyrazole, 2.5 g (0.01 mol) ofcobalt(II) acetate tetrahydrate, 0.66 g (2.68 mmol) of manganese(II)acetate tetrahydrate, 2.0 g (19.4 mmol) of 40 sodium bromide and 180 g(3.0 mol) of 100% pure acetic acid were heated to 130° C. in a 350 mlstirred autoclave. 20 bar of oxygen were injected at this temperature.The reaction started immediately. Oxygen was reinjected several times.After about 5 hours there was no further consumption of oxygen. Theautoclave 45 was cooled to room temperature and decompressed. Theresulting reaction mixture was concentrated in a rotary evaporator. Theresulting residue was recrystallized from 300 ml of 20% by weightaqueous acetic acid. Drying resulted in 44.1 g of5-chloro-1-methyl-4-pyrazolecarboxylic acid with a purity of 99.2%(HPLC). This corresponds to a yield of 82.6% of theory. The meltingpoint was 197° C.

EXAMPLE 11 Oxidation of 5-chloro-1-ethyl-4-methylpyrazole

The batch size and procedure corresponded to Example 10. 47.7 g (0.33mol) of 5-chloro-1-ethyl-4-methylpyrazole were employed. Drying resultedin 46.0 g of 5-chloro-1-ethyl-4-pyrazolecarboxylic acid with a purity of99.5% (HPLC). This corresponds to a yield of 79.5% of theory. Themelting point was 208° C.

EXAMPLE 12 Oxidation of 5-chloro-1,4-dimethylpyrazole

26.1 g (0.2 mol) of 5-chloro-1,4-dimethylpyrazole, 6.6 g (0.026 mol) ofcobalt(II) acetate tetrahydrate, 6.0 g (0.035 mol) of 47% strengthhydrobromic acid, 2.0 g (0.017 mol) of 30% strength hydrogen peroxideand 240 g (4.0 mol) of 100% pure acetic acid were heated to 90° C. in a350 ml stirred autoclave. 30 bar of oxygen were injected at thistemperature. The reaction started immediately. Oxygen was reinjectedseveral times. Oxygen consumption ceased after about 6 hours. Theautoclave was cooled to room temperature and decompressed. The resultingreaction mixture was concentrated in a rotary evaporator.Recrystallization from 150 ml of 20% by weight aqueous acetic acidafforded after drying 26.5 g of 5-chloro-1-methyl-4-pyrazolecarboxylicacid with a purity of 98.7% (HPLC). This corresponds to a yield of 81.5%of theory. The melting point was 195° C.

EXAMPLE 13 Preparation of 1-methyl-2-pyrazolin-5-one

10 g (0.0623 mol) of 5-chloro-1-methyl-4-pyrazolecarboxylic acid weredissolved in 100 g of 25% by weight sodium hydroxide solution (=0.623mol) in a 250 ml autoclave. The solution was heated at 175° C. for 6 h.The pressure rose to 6 bar during this. Cooling was followed bydecompression to atmospheric pressure. The reaction mixture was thenadjusted to pH 1.5 with 60% by weight sulfuric acid. CO₂ evolutionoccurred during this. After a few minutes, the pH was adjusted to 6.5with 25% by weight sodium hydroxide solution, and the resulting solutionwas evaporated to dryness in vacuo. The solid residue was transferredinto a 45 Soxhlet apparatus and extracted continuously with ethanol.Removal of the ethanol by distillation in vacuo resulted in 5.7 g of atarget compound with a purity of 98.9% (determined by gaschromatography). The melting point was 113° C. This corresponds to ayield of 92.3% of theory. The product was identified through a mixedmelting point with an authentic sample.

EXAMPLE 14 Preparation of1-ethyl-2-pyrazolin-5-one=5-hydroxy-1-ethylpyrazole

4 g of 5-chloro-1-ethyl-4-pyrazolecarboxylic acid were dissolved in 40 gof 25% by weight sodium hydroxide solution and reacted in analogy to theprocedure described in Example 1. The reaction temperature in the firstreaction stage was 170° C., and the reaction pressure was 7.5 bar. Thereaction lasted 8 h. Working up in the manner described for Example 1resulted in 2.3 g of the target compound with a purity of 99.7%(determined by gas chromatography). This corresponds to a yield of 89.4%of theory. The melting point was 88° C. The product was identified by amixed melting point with an authentic sample.

EXAMPLE 15 Preparation of 1-methyl-2-pyrazolin-5-one, workup byliquid/liquid extraction

10 g of 5-chloro-1-methylpyrazole-4-carboxylic acid were reacted as inExample 1 initially with 100 g of 25% by weight sodium hydroxidesolution and subsequently under acidic conditions. After the acidicreaction mixture had been neutralized to pH 6.5 with 25% by weightsodium hydroxide solution, the reaction mixture was transferred into aliquid/liquid extractor and extracted with isobutanol at the boilingpoint of the solvent. After isolation of the organic phase and removalof the isobutanol by distillation, 5.8 g of 1-methyl-2-pyrazolinoneremained (GC purity: 98.1%). The melting point was 112° C. The yield was92.5% of theory.

1. A process for preparing 1-substituted 5-chloro-4-methylpyrazoles ofthe formula I

in which R is C₁–C₈-alkyl or C₅–C₁₀-cycloalkyl, each of which optionallyhas one or more substituents, by reacting a 4-methylpyrazole of theformula II

 in which R has the abovementioned meanings, with chlorine, resulting ina mixture of compound I and a 1-substituted3,5-dichloro-4-methylpyrazoIe compound III

 in which R has the aforementioned meanings, wherein the compound III isseparated from the compound I, the compound III is dehalogenated to givethe compound II, and the latter is returned to the reaction of II withchlorine.
 2. A process as claimed in claim 1, wherein the dehalogenationis carried out with hydrogen in the presence of palladium as catalyst.3. A process as claimed in claim 2, wherein the catalyst is palladiumsupported on activated carbon.
 4. A process as claimed in claim 1,wherein compound III is combined before the dehalogenation with thecompound II to be chlorinated.
 5. A process for preparing 1-substitutedpyrazolones of the formula IV

which comprises preparing in a first reaction step a 1-substituted5-chloro-4-methylpyrazole of the formula I by a process as claimed inclaim 1, subsequently oxidizing the 4-methyl group in the compound I toa carboxyl group, reacting the 4-carboxy-5-chloropyrazole of the formulaV obtained in this way

in which R has the meanings stated in claim 1, with a molar excess ofalkali metal hydroxide in an aqueous reaction medium at elevatedtemperature, and subsequently adjusting a pH of ≦6 in the aqueousreaction medium by adding an acid.
 6. A process as claimed in claim 5,wherein the compound of the formula V is reacted with at least 3 mol ofalkali metal hydroxide based on 1 mol of the compound V.
 7. A process asclaimed in claim 5, wherein the reaction with aqueous alkali metalhydroxide is carried out at a temperature above 90° C.
 8. A process asclaimed in claim 5, wherein the acid is added at a temperature in therange from 0 to 100° C.
 9. A process as claimed in claim 5, wherein thedehalogenation is carried out with hydrogen in the presence of palladiumas catalyst.
 10. A process as claimed in claim 5, wherein the catalystis palladium supported on activated carbon.
 11. A process as claimed inclaim 5, wherein compound III is combined before the dehalogenation withthe compound II to be chlorinated.